Our observations suggest that the observed, reverse, vesicular transport of HRP across the endothelial cells of some blood vessels represents one of several possible mechanisms responsible for the removal of extravasated proteins and of edematous fluid from brain extracellular space. This reverse transport is accompanied by a disruption of the surface anionic layer and changed polarity of endothelial cells manifested by the relocation of alkaline phosphatase activity from luminal to abluminal plasmalemma. The newly described mechanism for transvascular route of serum protein removal may play a very significant role in various phases of resolution of vasogenic edema and therefore investigations concerning possible acceleration of such transvascular removal may be of importance in designing some therapeutic measures in vasogenic brain edema.